Cardiovascular System

The cardiovascular system is also called the circulatory system or the blood-vascular system. It is primarily responsible for transporting oxygen among many other important substances and nutrients throughout the body. The heart, a powerful pump, utilizes an intricate and extensive network of blood vessels to perform this function.

Anatomy of the Heart

Anatomical Location of the Heart

• Snugly enclosed within the middle mediastinum (medial cavity of thorax), which contains the
  • Heart
  • Pericardium
  • Great Vessels
  • Trachea
  • Esophagus
• Middle Mediastinum – located in the inferior mediastinum (lower than the sternal angle)
• Extends obliquely from 2nd rib → 5th intercostal space
• Anterior to Vertebrae
• Posterior to Sternum
• Flanked by 2 lungs
• Rests on the diaphragm
• 2/3 of its mass lies to the LHS of the midsternal line

The Pericardium (Coverings of the Heart)

• A double-walled sac
• Contains a film of lubricating serous fluid
• 2 Layers of Pericardium
  • Fibrous Pericardium
    • Tough, dense connective tissue
    • Protects the heart
    • Anchors it to surrounding structures
    • Prevents overfilling of the heart – if fluid builds up in the pericardial cavity, it can inhibit effective pumping. (Cardiac Tamponade)
  • Serous Pericardium (one continuous sheet with ‘2 layers’)
    • Parietal Layer – Lines the internal surface of the fibrous pericardium
    • Visceral Layer – (aka Epicardium) Lines the external heart surface

Layers of the Heart Wall 

• Epicardium
  • Visceral layer of serous pericardium
• Myocardium
  • Muscle of the heart
  • The layer that ‘contracts’
• Endocardium
  • Lines the chambers of the heart (endothelial cells)
  • Prevents clotting of blood within the heart
  • Forms a barrier between the O² hungry myocardium and the blood (blood is supplied via the coronary system)

Fibrous Skeleton of the Heart

• The network of connective tissue fibers (collagen & elastin) within the myocardium
• Anchors the cardiac muscle fibers + valves + great vessels.
• Reinforces the myocardium
• Provides electrical isolation
• 2 parts
  • Septum
    • Flat sheets separating atriums, ventricles & left and right sides of the heart
    • Electrically isolates the left & right sides of the heart (connective tissue = non-conductive)
      • Important for cardiac cycle
    • Interatrial septum/atrioventricular septum/interventricular septum
  • Ring
    • Rings around great vessel entrances & valves
    • Stops stretching under pressure 

Chambers & Associated Great Vessels

2 Atria (Superior) 

• Atrium = entryway
• On the superior aspect of the heart (above the ventricles)
• Each has a small, protruding appendage called auricles – increasing atrial volume
• Separated by Atrial Septum (Site of Fetal Shunt Foramen Ovale)
• Right Atrium
  • Ridged internal anterior wall – due to muscle bundles called pectinate muscles
  • Blood enters via 3 veins
    • Superior Vena Cava
    • Inferior Vena Cava
    • Coronary Sinus (collects blood draining from the myocardium)
• Left Atrium
• Blood enters via
  • The 4 pulmonary veins (O² blood)

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2 Ventricles (Inferior) 

• Vent = underside
• Thick, muscular Discharging Chambers
• The ‘pumps’ of the heart
• Trabeculae Carneae (crossbars of flesh) line the internal walls
• Papillary Muscles play a role in valve function
• Right Ventricle
  • Most of heart’s Anterior Surface
  • Thinner – responsible for the Pulmonary Circulation – Via Pulmonary Trunk
• Left Ventricle
  • Most of the heart’s Postero-Inferior Surface
  • Thicker – it is responsible for the Systemic Circulation – Via Aorta

Landmarks of the Heart

• Coronary Sulcus (Atrioventricular Groove)
  • Encircles the junction between the Atria & Ventricles like a ‘Crown’ (Corona)
  • Cradles the Coronary Arteries (R&L), Coronary Sinus, & Great Cardiac Vein
• Anterior Interventricular Sulcus
  • Cradles the Anterior Interventricular Artery (Left Anterior Descending Artery)
  • Separates the right & left Ventricles anteriorly
  • Continues as the posterior Interventricular Sulcus
• Posterior Interventricular Sulcus
  • Cradles the Posterior Descending Artery
  • Continuation of the Anterior Interventricular Sulcus
  • Separates the right & left ventricles posteriorly

Pathway of Blood through the Heart

The right side

• pumps blood through the pulmonary circuit (to the lungs and back to the left side of the heart)
• blood flowing through the pulmonary circuit gains oxygen and loses carbon dioxide, indicated by the color change from blue to red

The left side

• pumps blood via the systemic circuit to all body tissues and back to the right side of the heart
• blood flowing through the systemic circuit loses oxygen and picks up carbon dioxide (red to blue color change)

Coronary Circulation

• The myocardium’s own blood supply
• The shortest circulation in the body
• Arteries lie in epicardium – prevents the contractions inhibiting blood flow
• There is a lot of variation among different people

Arterial Supply

• Encircle the heart in the coronary sulcus
• Aorta → Left & Right coronary arteries
  • Left Coronary Artery → 2 Branches:

1. Anterior Interventricular Artery (aka. Left Anterior Descending Artery or LAD

• Follows the Anterior InterVentricular Sulcus
• Supplies Apex, Anterior LV, Anterior 2/3 of IV-Septum

2. Circumflex Artery

• Follows the Coronary Sulcus (aka. AtrioVentricular Groove)
• Supplies the Left Atrium + Lateral LV

• Right Coronary Artery → 2 (‘T-junction) Branches:
  • Marginal Artery:
    • Serves the Myocardium Lateral RHS of Heart
• Posterior Interventricular Artery:
  • Supplies posterior ventricular walls
  • Anastomoses with the Anterior Interventricular Artery (LAD)

Venous Drainage 

• Venous blood – collected by the Cardiac Veins (empties into the right atrium)
  • Great Cardiac Vein (in Anterior InterVentricular Sulcus)
  • Middle Cardiac Vein (in Posterior InterVentricular Sulcus)
  • Small Cardiac Vein (along Right inferior Margin)

Heart Valves

Ensure unidirectional flow of blood through the heart

2x Atrioventricular (AV) (Cuspid) Valves

• Location → at the 2 atrial-ventricular junctions
• Function → prevent backflow into the atria during contraction of ventricles
• Chordae tendineae (tendinous cords) “heart strings” – attached to each valve flap
  • Anchor the cusps to the Papillary Muscles protruding from ventricular walls.
    • Papillary muscles contract before the ventricle to tension the chordae tendineae
    • Prevent inversion of valves under ventricular contraction
• Tricuspid valve (right)
  • 3 flexible ‘cusps’ (flaps of endocardium + Conn. Tissue)
• Mitral valve (left)
  • (resembles the 2-sided bishop’s mitre [hat])

2x Semilunar (SL) Valves

• Located at the bases of both large arteries issuing from the ventricles
• Each consists of 3 pocket-like cusps resembling a crescent moon (semilunar = half moon)
• Open under Ventricular Pressure
• Pulmonary Valve
  • Between Right Ventricle & Pulmonary Trunk
• Aortic Valve
  • Between Left Ventricle & Aorta

Valve Positions during ventricular contraction (left) and relaxation (right)

Valve Sounds

1. “Lubb”

• Sound of AV valve closure
• M1 = Mitral component
• T1 = Tricuspid component

2. “Dupp”

• Sound of SL valve closure
• A2 = Aortic component
• P2 = Pulmonary component

Electrophysiology of the Heart

The Heartbeat

• Heart is a muscle and requires
  • O²,
  • Nutrients, and
  • Action Potentials to function
    • However, these neural signals don’t come from the brain;
    • Rather, the heart has its own conduction systems
      • allow heart to contract autonomously
    • Hence why a transplanted heart still operates (if provided with O² and nutrients)
• Cardiac Activity is coordinated:
  • To be effective, the atria & ventricles must contract in a coordinated manner
  • This activity is coordinated by the heart’s Conduction Systems
• The entire heart is electrically connected by:
  • Gap junctions
    • Allow action potentials to move from cell to cell
  • Intercalated discs
    • Support synchronized contraction of cardiac tissue

The Heart’s Conduction Systems

SA Node → AV Node → Bundle of His → R&L Bundle Branches → Purkinje Fibers → Myocyte Contraction

Conductile Cardiac Cell Physiology (SA/AV Node Cells)

• Action Potentials: Slow ‘Pacemaker’ Type
• Have UNSTABLE Resting Membrane Potentials → spontaneous electrical activity
  • Spontaneously depolarize to threshold
    • This gradual depolarisation is called a ‘Prepotential’
    • Due to leaky Na⁺ membrane ion channels
    • Therefore – firing frequency depends on Na⁺ movement
  • Depolarisation:
    • Once threshold is reached, Ca²⁺ channels open
    • → Influx of Ca+
    • → Causes an action potential
  • Repolarisation:
    • Once peak MP is reached, Ca⁺ channels close, K⁺ channels open
    • → K+ Efflux makes MP more negative

• → Causes repolarisation
• (Na⁺ brings to threshold, but Ca⁺ is responsible for Depolarisation.)
• With a Hierarchy of control over the heart
  • Hierarchy based on natural intrinsic rate (fastest node (SA node) takes control)

Contractile Cardiac Cell Physiology (Purkinje Fibers & Myocytes)

• Action Potentials: Fast ‘Non-Pacemaker’ Type
• Have STABLE Resting Membrane Potentials
  • Resting Membrane Potential (MP):
    • Na⁺ & Ca⁺ channels are closed
    • Any positive change to MP causes Fast Na⁺ channels to open → positive feedback → threshold
  • Depolarisation:
    • If MP reaches threshold, all Fast Na⁺ channels open;
    • → Massive influx of Na⁺ into cell
    • → Membrane depolarises
  • Plateau:
    • Fast Na⁺ channels inactivate
    • → The small downward deflection is due to Efflux of K⁺ ions
    • → Action potential causes membrane Voltage-Gated Ca⁺ channels to open
      • This triggers further Ca⁺ release by the sarcoplasmic reticulum into the sarcoplasm (“Ca induced Ca Release”)
        • This increased myoplasmic Ca⁺ causes muscular contraction.
      • Plateau is sustained by influx of Ca⁺, balanced by efflux of K⁺ ions
  • Repolarization:
    • Influxing Ca⁺ channels close, the effluxing K⁺ channels remain open
      • → Result is a net outward flow of positive charge. → Downward Deflection
      • → As the MP falls, more K⁺ channels open, accelerating depolarization
      • → Membrane Repolarizes & most of the K⁺ channels close
  • What happens to the excess ions?
    • Excess Na⁺ in the cell from depolarization is removed by the Na/K-ATPase
    • Deficit of K⁺ in the cell from repolarization is replaced by the Na/K-ATPase
    • Excess Ca⁺ from the Plateau Phase is eliminated by a Na/Ca Exchanger

NOTE:

There is considerable delay between myocardial contraction and the action potential.

Refractory Periods

In cardiac muscle, the Absolute Refractory Period continues until muscle relaxation

• Therefore, summation is not possible → tetany cannot occur (critical in heart)
• i.e., the depolarized cell will not respond to a 2nd stimulus until contraction is finished

Absolute Refractory Period 

• Approximately 200ms
• Duration: from peak → plateau → halfway-polarized 

Relative Refractory Period 

• Na⁺ channels are closed – but can still respond to a stronger-than-normal stimulus
• Approximately 50ms
• Duration: last half of repolarization 

The Sinoatrial (SA) Node

• The “Pacemaker” of the Heart: Unregulated Rate: 90-100bpm; however
  • Parasympathetic NS lowers heart rate → keeps Normal Resting HR at 70bpm
  • Sympathetic NS raises heart rate
• Location
  • Posterior Wall of the Right Atrium near the opening of the Superior Vena Cava
• Nature of Action Potentials
  • Continually Depolarizing 90-100bpm
  • Takes 50ms for Action-Potential to reach the AV Node
• Role in Conduction Network
  • Sets the pace for the heart as a whole
• Portion of Myocardium Served
  • Contracts the Right & Left Atrium

The Atrioventricular (AV) Node

• 2nd in Command: Slower than the SA Node: 40-60bpm
• Location
  • Inferior portion of the Interatrial Septum
  • Directly above the Tricuspid Valve
• Nature of Action Potentials
  • Continually Depolarizing – but slower than the SA Node (40-60 bpm)
• Role in Conduction Network
  • To delay the impulse from the Sinoatrial Node → bundle branches;
  • Delay allows the atria to empty their contents before Ventricular Contraction
  • Delay: approx. 100ms
• Portion of Myocardium served
  • Conducts the SA Node impulses to the Purkinje Fibers (which supply the ventricular walls)

Bundle Branches (Bundles of His)

• 3rd in Command: slower than AV & SA Nodes: 20–40 bpm
• Location
  • Fork of branches – superior portion of interventricular septum 
• Nature of Action Potentials
  • Continually depolarizing – slower than AV & SA Nodes (20–40 bpm)
• Role in conduction network 
  • Serves as the only connection between the 2 atria & 2 ventricles
  • The 2 atria & 2 ventricles are isolated by the fibrous skeleton and lack of gap junctions
• Portion of the myocardium served 
  • Transmits impulses from the AV node to the R&L Bundle branches 
  • Then along the interventricular septum → apex of the heart 

Purkinje Fibers 

• Specialized Myocytes with very few myofibrils → don’t contract during impulse transmission
• Location
  • The Inner Ventricular Walls of the Heart – just below the Endocardium
  • Begin at the heart apex, then turn superiorly into the Ventricular Walls
• Nature of Action Potentials
  • Conductile
  • Resembles those of Ventricular Myocardial Fibers
    • However the Depolarisation is more pronounced & the Plateau is longer.
    • Long Refractory period
  • Capable of Spontaneous Depolarisation – 15bpm
• Role in Conduction Network
  • Carry the contraction impulse from the L & R Bundle Branches to the Myocardium of the Ventricles
  • Causes Ventricles to contract
• Portion of Myocardium served
  • R & L Ventricles

Effect of the Autonomic Nervous System (ANS)

Although the heart can operate on its own, it normally communicates with the brain via the autonomic nervous system

Parasympathetic Nervous System 

• Innervates SA & AV Nodes → slows heart rate
• Direct Stimulation → Releases Acetylcholine → Muscarinic receptors in SA/AV Nodes
  • Causes increased K⁺ permeability (Efflux) → Hyperpolarizes the cell
    • Cell takes longer to reach threshold → Lower Heart Rate

Sympathetic Nervous System

• Innervates the SA & AV Nodes & ventricular muscle
  • → Raises Heart Rate
  • → Increases force of contraction
  • → Dilates arteries
• Indirect stimulation → Sympathetic nerve fibers release Noradrenaline (Norepinephrine) at their cardiac synapses → Binds to Beta 1 Receptors on Nodes & Muscles →
  • Initiates a cyclic AMP pathway → Increases Na⁺ + Ca⁺ permeability in nodal tissue & increases Ca⁺ permeability_{(Membrane & SR)} in muscle tissue
• Effects on Nodal Tissue
  • ++Permeability to Na⁺ → more influx of Na⁺ → Membrane ‘drifts’ quicker to threshold → Increased heart rate
  • ++Permeability to Ca+ → more influx of Ca+ → Membrane depolarisation is quicker → Increased heart rate
• Effects on Contractile Tissue
  • ++ Membrane permeability to Ca⁺ → More influx of Ca⁺ →
  • ++Sarcoplasmic reticulum permeability to Ca⁺ → Efflux of Ca⁺ into cytoplasm→
    • Increases available Ca⁺ for contraction → Contractile force increases

Electrocardiogram (ECG) Physiology 

What is an ECG?

• A recording of all action potentials by nodal & contractile cells in the heart at a given time 
  • It i NOT a single action potential 
  • A “lead” refers to a combination of electrodes that form an imaginary line in the body, along which the electrical signals are measured
    • i.e., a 12 ‘lead’ ECG usually only uses 10 electrodes 
• Measured by voltmeters → record electrical potential across 2 points
  • 3x bipolar leads: measure voltages between the arms or between an arm and a leg
    • I = LA(+) RA(-)
    • II = LL(+) RA(-)
    • III = LL(+) LA(-)
  • 9x unipolar leads: look at the heart in a ‘3D’ image 
• Graphic output
  • X-axis: time 
  • Y-axis: amplitude (voltage) – proportional to number and size of cells 
• Understanding waveforms 
  • When a Depolarisation Wavefront moves toward a positive electrode, a Positive deflection results in the corresponding lead.
  • When a Depolarisation Wavefront moves away from a positive electrode, a Negative deflection results in the corresponding lead.
  • When a Depolarisation Wavefront moves perpendicular to a positive electrode, it first creates a positive deflection, then a negative deflection.

How Each Wave Segment is Formed

	P-Wave Depolarization of the atria  Presence of this wave indicates the SA node is working
	PR-Segment Reflects the delay between SA & AV nodes Atrial contraction is occurring at this time
	Q-Wave Interventricular septum depolarization  Wave direction (see blue arrow) is perpendicular to the main electrical axis → results in a biphasic trace Only the negative deflection is seen due to signal cancellation by atrial repolarization  Sometimes this wave isn’t seen at all
	R-Wave Ventricular depolarization  Wave direction (see blue arrow) is the same as the main electrical axis → positive deflection  R-wave amplitude is large due to sheer numbers of depolarizing myocytes
	S-Wave Depolarization of the myocytes at the last of the Purkinje Fibers  Wave direction (black arrow) opposes the main electrical axis → negative deflection  This wave is not always seen
	ST-Segment Ventricular contraction is occurring at this time Due to the lag between excitation and contraction
	T-Wave Ventricular repolarization  Positive deflection despite being a repolarization wave – because repolarization waves travel in the opposite direction to depolarization waves

Relating ECG Waves to Events in the Cardiac Cycle 

• Contractions of the heart ALWAYS lag behind impulses seen on the ECG
• Fluids move from high → low pressure 
• Heart valves ensure a unidirectional flow of blood 
• Coordinated contraction timing – critical for correct flow of blood 

The Heart’s Electrical Axis 

• Refers to the general direction of the heart’s depolarization wavefront (or ‘mean electrical vector’) in the frontal plane
  • It is usually oriented in a ‘Right Shoulder to Left Leg’ direction
• Determining the electrical axis from an ECG trace
  • 3 methods
    • Quadrant Method (the one you’re concerned with)
    • Peak Height Measurement Method
    • The Degree Method

The Quadrant Method 

LEAD 1	LEAD aVF	QUADRANT	AXIS
+	+		Normal(0 to +90°)
+	–		**Possible LAD (0 to -90°)
–	+		RAD (+90° to 180°)
–	–		Extreme Axis(-90° to 180°)

• Normal Axis. QRS positive in I and aVF (0 90 degrees). Normal axis is actually 30 to 105 degrees.
• Left Axis Deviation (LAD). QRS positive in I and negative in aVF, 30 to 90 degrees
• Right Axis Deviation (RAD). QRS negative in I and positive in aVF, +105 to +180 degrees
• Extreme RAD. QRS negative in I and negative in aVF, +180 to +270 or 90 to 180 degrees

Algorithm for Looking at ECGs

• Check Pt ID
• Check voltage & timing
  • 25mm/sec
  • 1 large square = 0.2s (1/5sec)
  • 1 small square = 0.04s
• What is the rate?
  • 300/number of large squares between QRS Complexes
    • Tachycardia >100bpm
    • Bradycardia <60bpm
• What is the rhythm?
  • Sinus? (are there P-Waves before each QRS complex)
  • If not sinus?
    • Is it regular?
    • Irregular?
    • Irregularly Irregular (AF)
    • Brady/Tachy
• Atrial Fibrillation
  • Irregularly Irregular
  • P-Waves at 300/min
• QRS
  • Is there one QRS for each P-wave?
  • Long PR Interval? (1st degree heart block)
  • Missed Beats? (Second degree block)
  • No relationship? Complete heart block
• Look for QRS Complexes
  • How wide – should be < 3 squares
  • If wide – It is most likely Ventricular
  • (Sometimes atrial with aberrant conduction (LBBB/RBBB)
  • IF Tachycardia, & Wide Complex → VT is most likely. (If hypotensive → Shock; if Normotensive → IV Drugs)
• Look for T-Waves
  • Upright or Inverted
• Look at ST-Segment
  • Raised, depressed, or inverted
  • ST Distribution → Tells you which of the coronaries are blocked/damaged
    • Inferior ischaemia (II, III, AVF)
    • Lateral ischaemia (I, II, AVL, V5, V6)
    • Anterior ischaemia (V, leads 2-6)
  • NOTE: Normal ECG Doesn’t exclude infarct.
  • ST Depression → Ischaemia
  • ST Elevation → Infarction
  • If LBBB or Paced, you CANNOT comment on ST-Segment

Mechanical Events of the Cardiac Cycle

Structure-Function Relationship of the Heart

• The Myocardium is essentially one long muscle orientated in a spiral-like fashion
  • This allows the heart to be electrically integrated
  • Allows the heart to ‘wring out’ the blood within it
  • This setup facilitates a strong pumping action 

Terms

• Systole = Myocardial Contraction
• Diastole = Myocardial Relaxation
• Stroke Volume = Output of Blood from the heart per contraction (≈80mL of blood)
• Heart Rate = #Heart Beats/Minute
• Cardiac Output
  • Volume of blood ejected from the heart per minute (Typically ≈5L/min)
  • Cardiac Output = Heart Rate x Stroke Volume
  • Chronotropic Influences
    • Affect heart rate
  • Inotropic Influences
    • Affect contractility (& stroke volume)
  • Dromotropic Influences
    • Affect AV Node delay
• End Diastolic Volume = Ventricular volume at end of Diastole (When ventricle is fullest)
• End Systolic Volume = Ventricular volume after Contraction (Normal ≈ 60-65%)
• Preload = The degree of stretching of the heart muscle during Ventricular Diastole
  • (↑Preload = ↑cross linking of myofibrils = ↑Contraction (“Frank Starling Mechanism”)
• Afterload = The ventricular pressure required to eject blood into aorta/pulmonary artery
  • (↑Afterload = ↓SV due to ↓ejection time)

Overview of the Cardiac Cycle

Phase 1 – Atrial Contraction (Systole) + Ventricular Filling (Diastole) 

• Contraction of atria 
  • → intra-atrial pressure increases
  • → blood pushed into ventricles through AV valves 
• Note: ventricles are already 70% full from passive venous filling 
• At the end of atrial systole, ventricles have EDV (end diastolic volume) ≈130mL

Phase 2 – Ventricular Systole

AV Valves Close

• Ventricular pressure exceeds atrial pressure → AV valves shut 
• Brief period of isovolumetric contraction
  • Where ventricular pressure rises, but volume stays constant 
  • The beginning of ventricular systole
  • All valves are still closed 

Semilunar Valves Open 

• Ventricular pressure exceeds aortic/pulmonary pressure → blood ejected
  • ≈80mL of blood ejected each time (Stroke Volume) 
  • Ventricular volume decreases

Semilunar Valves Close

• Ventricular pressure then falls below aortic/pulmonary pressure → semilunar valves close
  • Sudden closure of semilunar valves causes the dicrotic notch
    • Result of elasticity of the aorta & blood rebounding off the closed SL valve 
    • Causes a slight peak in aortic pressure 
• Note: ventricles never fully empty
  • ESV (End Systolic Volume) = amount of blood left in ventricles → 50mL

Phase 3 – Ventricular Diastole 

• Ventricles relax → Ventricular pressure falls below atrial pressure → AV valves open:
  • Blood → from Atria into ventricles
  • (NOTE: Passive filling from venous return is responsible for 70% of ventricular filling.)

Cardio-Dynamics

Cardiac Output

• Useful when examining cardiac function over time
• Determined by 2 things
  • Stroke Volume
  • Heart Rate

Cardiac Output_(mL/min) = Stroke Volume X Heart Rate

• Average CO ≈ 5L/min (i.e.: The entire blood supply circulates once per minute)
• Cardiac Output is regulated such that peripheral tissues receive adequate blood supply

Heart Rate

• Depends on tissue-satisfaction with nutrients and O₂
• Terms
  • Bradycardia. HR slower than normal (too fast → stroke volume & CO suffer) 
  • Tachycardia. HR faster than normal 

5 Things that Affect Heart Rate

• Alterations in SA Node Firing 
  • SA node is the pacemaker; therefore, change it rate → change heart rate
    • → change CO 
• Autonomic Nervous System
  • Parasympathetic (Vagus Nerve)
    • Decrease HR (negative chronotropic effect) 
    • Increase AV node delay (negative dromotropic effect) 
    • NOTE: ONLY A TINY EFFECT ON CONTRACTILITY 
  • Sympathetic (Sympathetic Chains)
    • Increase HR (positive chronotropic effect) 
    • Increase force of contraction (positive inotropic effect) 
• Reflex Controls 
  • Bainbridge Reflex (Atrial Walls)
    • Where an ↑Venous Return → ↑Heart Rate
    • (Stretch of Atrial Walls → Stretch Receptors → Sympathetic NS → ↑HR)
    • Responsible for 40-60% of HR increases
  • Chemoreceptor Reflex
    • ↓Low O₂ or ↑CO₂ in Peripheral-Tissue → ↑HR & ↑Respiratory Rate
  • Baroreceptor Reflex (Aortic & Carotids)
    • Where an ↑BP → ↓HR & ↓Contractility (+ Vasodilation)
    • 2 Main Baroreceptors
      • Aortic → Vagus Nerve → CV Center (medulla/pons)
      • Carotid → Hering’s Nerve → CV Center (medulla/pons)
    • Constantly responds to blood pressure change
      • (via stretch in vessel walls)
      • More stretch = More firing: leads to:
        • Parasympathetic activation
        • Sympathetic deactivation
    • Receptors never silent – constantly signaling
    • Quick to respond
    • In hypertension → receptors recalibrate to the higher BP
    • Changes HR accordingly

• Atrial Node Stretching (similar to baroreceptor reflex, but in the atrium)
  • Venous return fills atria with blood
    • When Venous Return ↑, Atrial Walls Stretch → Stretches SA-Node
  • Stretching of SA node cells → More rapid depolarisation → ↑HR
  • Responsible for 15% of HR increases
  • Influenced by
    • Arterial Pressure
    • Peripheral Compliance
    • Local Blood Flow
    • Capillary Exchange
• Chemical Regulation 
  • Hormones
    • Adrenaline 
    • Thyroxine 
    • Insulin 
  • Ions
    • Na⁺
    • K⁺
    • Ca²⁺

Other Factors that Affect HR 

• Age (old → lower resting HR) 
• Gender (females → higher resting HR) 
• Physical fitness (fit → lower resting HR) 
• Temperature (hot → higher resting HR) 

Stroke Volume

• Blood output per heartbeat
• Useful when examining the efficiency of a single cardiac cycle

Stroke Volume (SV) = End Diastolic Volume (EDV) – End Systolic Volume (ESV)

• Therefore, Stroke Volume is ↑ by
  • ↑ Ventricular filling time (duration of ventricular diastole)
  • ↑ Venous return
  • ↓ Arterial BP (a high arterial BP → harder to eject blood → ESV increases)
  • ↑ Force of ventricular contraction

2 Things that Affect Stroke Volume 

Preload

• The degree of stretching of the heart muscle during Ventricular Diastole
• Caused by amounts of blood from venous return
• Influenced by
  • Arterial Pressure
  • Peripheral Compliance
  • Local Blood Flow (depending on the demands of those tissues)
  • Capillary Exchange.
• Preload ↑ as EDV↑ (directly proportional)
  • ↑End Diastolic Volume = ↑Stroke Volume (Frank-Starling Law)
• Affects % of actin/myosin contact in myocytes→ Affects cross-bridge cycling:
  • → Affects muscle’s ability to produce tension
  • Preload varies with demands placed on the heart
• Contractility
  • Inotropy
  • Force produced during contraction at a given preload
  • Influences End Systolic Volume (↑Contractility = ↓ESV)

Afterload

• Back pressure exerted by arterial blood
• The tension needed by ventricular contraction to open semilunar valve
  • i.e., The pressure the heart must reach to eject blood
• ↑Afterload = ↑ESV = ↓SV
• Afterload is increased by anything that restricts arterial blood flow

Hemodynamics

Relationship between Flow, Pressure, Resistance

• Flow is directly proportional to pressure gradient between 2 points (change in pressure)
• Flow is inversely proportional to resistance
• Resistance is far more important in determining local blood flow versus the pressure gradient 

Blood Flow Rate 

• The Amount of blood flowing through a vessel/organ/system per unit time (mLs/min)
  • Determined by pressure gradient & resistance, NOT velocity
• Systemic Blood Flow = Cardiac Output (relatively constant)
• Specific Organ Blood Flow – may vary widely due to its immediate needs

Velocity of Flow 

• Velocity of Flow = SPEED of flowing blood (mm/sec)
• e..g, A constricted vessel will have a lower flow rate, but a higher velocity of flow (i.e., Garden hose)
• Note: Velocity tends to change by a greater magnitude than the change in Flow Rate

Blood Pressure

• The Pressure exerted on the vessel wall by contained blood (mmHg)
• Decreases with distance from heart (arterial system)
• Decreases with 10%+ decrease blood volume
• Increases with vessel constriction (provided same blood volume)

Resistance

• The amount of friction blood encounters as it passes through the vessels
• 3 factors influencing resistance
  • Blood Viscosity (↑Viscosity = ↑Resistance) (Fairly Constant)
  • Total Vessel Length (longer vessel = ↑ resistance) (Fairly Constant)
  • Vessel Diameter (thinner vessel = ↑resistance) (Frequently Changes)
    • Most responsible for changes in BP
• Systemic Vascular Resistance = Combination of the Above Factors

Effects of Vessel Diameter (Vasomotion) on Flow Rate 

• The flow rate is directly proportional to the 4th power of the vessel diameter
• i.e., Small changes in vessel diameter → Changes flow rate by an exponent of 4
• Poieuille’s Law 

Effects of Vessel Diameter (Vasomotion) on Flow Velocity

• Flow rate is inversely proportional to the vessel’s cross-sectional area
• i.e., An ɑ x increase in cross-sectional area → decrease in flow velocity by a factor of ɑ

Blood Pressure Physiology

Factors Influencing Blood Pressure

• Cardiac Output
  • ↑Cardiac Output = ↑ BP
• Peripheral Resistance
  • Causes back pressure in blood (arterial system)
  • e.g., In obesity, peripheral resistance increases.
• Blood Volume
  • (assuming constant vessel diameters) ↑Blood Volume = ↑BP
  • Its effect depends on vessel compliance

BP = Cardiac Output X Total Peripheral Resistance

Types of Blood Pressure

Systolic 

• Peak aortic pressure reached during ventricular systole
• A function of
  • Peak rate of ejection
  • Vessel wall compliance
  • Diastolic BP
• Normal = 120mmHg

Diastolic 

• Lowest aortic pressure reached during ventricular diastole, due to blood left after peripheral runoff
• A function of
  • Blood volume
  • Heart rate
  • Peripheral resistance
• Normal = 80mmHg

Pulse Pressure*

• Pulse Pressure = Systolic Pressure – Diastolic Pressure
• e.g., 120mmHg – 80mmHg
• Normal = 40mmHg
• If lower: may be an indication of Aortic Stenosis or Atherosclerosis (slowed peripheral runoff)

Mean Arterial Pressure*

• MAP = Diastolic Pressure + 1/3(Pulse Pressure)
• The pressure that propels blood to the tissues – maintains tissue perfusion
  • Maintains flow through capillary beds
• Must be high enough to overcome peripheral resistance (if not, blood doesn’t move)
• Finely controlled

3 Main Regulators of Mean Arterial Pressure

Autoregulation (at the tissue level) 

• Localized automatic vasodilation/constriction at the tissue level
  • Allows control of flow within a single capillary bed
  • Ensures perfusion of the ‘needy’ tissues
• Metabolic controls → Vasodilation
  • Low oxygen/nutrient levels
  • Nitric Oxide
  • Endothelin
  • Inflammatory chemicals: histamine/kinins/prostaglandins
• Myogenic control → Vasoconstriction
  • Sheer stress: Vascular smooth muscle responds to passive stretch (↑vascular pressure) with increased tone
    • Prevents excessively high tissue perfusion that could rupture smaller blood vessels
  • Reduced stretch promotes vasodilation → flow increases

Neural Mechanisms

• Vasomotor Center (medulla) 
  • Take info from receptors
    • Baroreceptors (primarily)
    • Chemoreceptors (lesser degree)
  • Transmit impulses via sympathetic nervous system
    • ↑ sympathetic activity = vasoconstriction = ↑ BP
    • ↓ sympathetic activity = vasodilation = ↓ BP
• Cardiovascular Centers of the ANS 
  • Sympathetic → ↑HR & Contractility → ↑MAP
  • Parasympathetic → ↓Heart Rate → ↓MAP

Endocrine Mechanisms (Kidney Level) 

• More for long-term BP & blood-volume regulation
• Antidiuretic Hormone (ADH)
  • Aka vasopressin
  • Released due to low blood volume
  • ADH → Water Retention Increased → ↑MAP
• Angiotensin II
  • Released due to low blood pressure
  • Potent vasoconstrictor
  • Increases cardiac output & blood volume
  • Angiotensin II → Vasoconstriction → ↑MAP
• NOTE: ‘ACE’ (Angiotensin I Converting Enzyme) activates it to Angiotensin II. Hence ‘ACE-Inhibitors’ are often used as AntiHypertension medicine)
• Erythropoietin
  • Released due to low pressure & low O₂ levels
  • Increases RBC production to increase blood volume
  • EPO → Hematopoiesis → ↑Blood Volume → ↑MAP
• Natriuretic Peptides (Released by the heart)
  • Released by the heart due to high blood pressure & volume
  • ↑Stretch on Heart → NP Release → ↑Diuresis → Reduces BP & Volume
  • Also inhibits ADH & Angiotensin II → Reduces BP & Volume

Anatomy & Physiology of Blood Vessels

Introduction to Blood Vessels

3 Classes

• Arteries → carry blood away from the heart
  • Elastic Arteries
    • e.g., Aorta & major branches (Conducting Vessels)
  • Muscular Arteries
    • e.g., Coeliac trunk & renal arteries (Distributing Vessels)
  • Arterioles
    • e.g., Intra-organ arteries (Resistance Vessels)
  • Terminal Arteriole
    • e.g., Afferent arteriole in kidney
• Capillaries → intimate contact with tissue; facilitate cell nutrient/waste transfer
  • Vascular shunt
  • True capillaries
• Veins → carry blood back to the heart
  • Post-capillary venule (union of capillaries) 
  • Small veins & large veins
    • Capacitance vessels
    • 65% of body’s blood is venous

Relationships between Vessel Diameter, Cross-Sectional Area, Local Blood Pressure, and Velocity of Flow 

Blood Vessel Structure

3-layered wall 

Tunica Intima 

• i.e.,  The layer in intimate contact with the blood (luminal)
• Consists of the endothelium (simple squamous epithelium)
• Larger vessels also have a sub-endothelial layer

Tunica Media

• Middle and thickest layer (smooth muscle + elastin)
  • Circulating smooth muscle
  • Sheets of elastin
• Regulated by sympathetic nervous system + chemicals
• Contraction/dilation maintains blood pressure

Tunica Externa

• Outermost layer (Loose collagen fibers)
• NOTE: Also contains nerve fibers, lymphatics, and vasa vasorum (in larger vessels)

The Arterial System

Elastic (Conducting) Arteries

• The aorta + its major branches
• Thick-walled
• Large lumen = low resistance
• Highest proportion of elastin
  • Withstands pressure fluxes
  • Smooths out pressure fluxes
  • ‘Stretch’ = potential energy → helps propel blood during diastole

Muscular (Distributing) Arteries 

• Distal to elastic arteries
• Deliver blood to specific body organs
• Diameter: 0.3mm→1cm
• Thickest tunica media
  • Due to smooth muscle
• Highest proportion of smooth muscle
  • Are active in vasoconstriction
  • Are therefore less distensible (less elastin)

Arterioles

• Smallest arteries
• Larger arterioles have all 3 tunics (intima/media/externa)
  • Most of the tunica media is smooth muscle
• Smaller Arterioles
  • Lead to capillary beds
  • Little more than 1 layer of smooth muscle around the endothelial lining
• Autoregulation of diameter
  • Controlled by
    • Neural (electrical) signals
    • Hormonal signals
      • Noradrenaline
      • Epinephrine
      • Vasopressin
      • Endothelin-1
    • Local chemicals
  • Controls blood flow to capillary beds
    • When constricted – tissues served are bypassed
    • When dilated – tissues served receive blood
• Biggest controller of blood pressure

The Capillary System

• Smallest blood vessels – microscopic
• Thin, thin walls 
• Tunica intima only (i.e., only 1 layer thick)
• Average length = 1mm
• Diameter: the width of a single RBC
  • RBC’s flow through capillaries in single file
  • RBC’s shape allows them to stack up efficiently against each other
• Penetrate most tissues, except:
  • Tendons
  • Ligaments
  • Cartilage
  • Epithelia
• Main role
  • Exchange of gases/nutrients/hormones/wastes
  • Exchange occurs between blood & interstitial fluid

Capillary Beds

• Capillaries are only effective in large numbers
  • Form networks called ‘capillary beds’
• Facilitates microcirculation
  • Blood flow from an Arteriole → Venule
  • Consist of 2 types of vessels
    • Vascular Shunt
      • From metarteriole → thoroughfare channel
      • Short vessel – directly connects arteriole with venule
    • True Capillaries
      • The ones that actually take part in exchange with tissues
      • Usually branch off the metarteriole (proximal end of vascular shunt)
      • Return to the thoroughfare channel (distal end of vascular shunt)
      • Precapillary Sphincters
        • Smooth muscle cuffs
        • Surround the roots of each true capillary (arterial ends)
        • Regulates blood flow into each capillary
        • i.e., Blood can either go through capillary or through the shunt
• A capillary bed may be flooded with blood or bypassed, depending on conditions in that organ

3 Types of Capillaries

Continuous Capillaries

• ‘Continuous’ = uninterrupted endothelial lining
• Adjacent cells form intercellular clefts
  • Joined by incomplete-tight-junctions
  • i.e., Allow limited passage of fluids & solutes
• NOTE: In the brain, the tight-junctions are complete → blood brain barrier

Fenestrated Capillaries 

• Endothelial cells are riddled with oval pores (fenestrations = windows)
  • Much more permeable to fluids & solutes than continuous capillaries
• Abundant wherever active absorption/filtration occurs
  • Intestines
  • Kidneys
  • Endocrine organs (allow hormones rapid entry to blood)

Sinusoids (Sinusoidal Capillaries) 

• aka  “leaky capillaries”
• Found ONLY in
  • Liver
  • Bone marrow
  • Lymphoid tissues
  • Some endocrine organs
• Large irregularly-shaped lumens
• Usually fenestrated
• ‘Discontinuous’ = interrupted by Kupffer cells
  • Remove & destroy bacteria
• Intercellular clefts → larger + have fewer tight junctions
  • Allow large molecules & leukocytes passage through to interstitial space

The Venous System

• Vessels carry blood back towards the heart (from capillary beds)
• Vessels gradually increase in diameter & thickness towards the heart

2 Types

Venules

• Formed by union of capillaries (post-capillary venules)
• Consist entirely of endothelium
• Extremely porous
• Allows passage of
  • Fluid 
  • White blood cells (migrate through wall into inflamed tissue)
• The larger venules
  • Have 1 or 2 layers of smooth muscle (i.e., tunica media)
  • Have a thin tunica externa as well

Veins

• Formed by union of venules
• 3 distinct tunics (but walls thinner than corresponding arteries)
  • Thinner walls due to lower blood pressure
• Tunica media
  • Poorly developed
  • Some smooth muscle
  • Some elastin
  • Tend to be thin even in large veins
• Tunica externa
  • Heaviest layer (thicker than media)
  • Thick longitudinal collagen bundles
  • Thick elastic networks
• Lumens larger than corresponding arteries
  • The reason 65% of the body’s blood is in the veins
  • Therefore veins: aka “capacitance vessels”
• Lower blood pressure than arteries
  • Require structural adaptations to get blood → heart:
    • Large lumen (low resistance)
    • Valves
• Venous valves
  • Folds of tunica intima (resemble semilunar valves)
  • Prevent blood flowing backward
  • Ensures unidirectional flow
  • Often have to work against gravity
  • If faulty, causes thrombosis (e.g., varicose veins)

Fetal Circulation 

• “Bypasses” / “shunts” of fetal circulatory system
• All of these “shunts” are occluded at birth due to pressure changes

Ductus Venosus

• Directs the oxygenated blood from the placental vein into inferior vena cava → heart
• Partially bypasses the liver sinusoids

Foramen Ovale

• An opening in the interatrial septum loosely closed by a flap of tissue
• Directs some blood entering the right atrium into the left atrium → aorta
• Partially bypasses the lungs
• NOTE: Foramen ovale can take up to 6 months to close 

Ductus Arteriosus

• Directs most blood from right atrium of the heart directly into aorta
• Partially bypasses the lungs

Fluid Movements across a Vessel

• Determined by the balance of 2 forces
• Hence, fluid is forced out at arterial end, and reabsorbed at venous end
• The amount of fluid forced out = determined by the balance of net hydrostatic & osmotic forces
  • i.e., Net Filtration Pressure = Net Hydrostatic Pressure – Net Osmotic Pressure 

Capillary Hydrostatic Pressure

• The force the blood exerts against the capillary wall
• Hydrostatic pressure = capillary blood pressure ≈ 35 mmHg_{Arterial End} /15 mmHg_{Venous End}
• Tends to force fluids through the capillary’s intercellular clefts (between endothelial cells)
  • Capillary hydrostatic pressure drops as blood flows from arteriole → venule
• Net hydrostatic pressure = Capillary Hydrostatic Pressure – Interstitial Hydrostatic Pressure
  • NOTE: Interstitial Hydrostatic Pressure ≈ 0 mmHg

Colloid Osmotic Pressure

• Opposes hydrostatic pressure
• Due to large, non-diffusible molecules (plasma proteins) drawing fluid into capillaries
• Typically ≈ 25 mmHg
  • Relatively constant at both arterial & venous ends
• Net Osmotic Pressure = Capillary Osmotic Pressure – Interstitial Osmotic Pressure
  • NOTE: Interstitial Osmotic Pressure ≈ 1 mmHg

Edema

• Abnormal accumulation of fluid in the interstitial space (i.e., tissue swelling)
• Caused by increase in flow of fluid → out of vessel or lack of reabsorption → into blood vessel
• Usually reflects an imbalance in colloid osmotic pressure on the 2 sides of the capillary membrane
  • e.g., Low levels of plasma protein (reduces amount of water drawn into capillaries
• Contributing factors
  • High BP (Hydrostatic Pressure)
    • Can be due to incompetent valves
    • Localized blood vessel blockage
    • Congestive heart failure (pulmonary edema – due to blockage in pulmonary circuit)
    • High blood volume
  • Capillary Permeability
    • Usually due to an inflammatory response

Injuries to Blood Vessels

Atherosclerosis

• Formation of fatty plaques in the subendothelial layer
• Fatty plaques begin to ulcerate 

Aneurysms

• Elastic arteries can lose their elasticity 
• Due to having thinner walls, they’re more prone to aneurysm formation (bulging & potentially rupturing)
  • Result in pooling of blood → eventual rupture 

Dissections

• Blood builds up between the layers of the wall & eventually press the vessel closed

 Physiology of Hypertension

What is Hypertension? 

• Consistent diastolic of +90mmHg AND/OR 
• Consistent systolic of +140mmHg
• A risk factor for other diseases
  • Coronary artery disease 
  • Stroke 
  • Heart failure 
  • Renal failure
  • Peripheral vascular disease 
• Usually asymptomatic 
• Often misdiagnosed due to 

Classifications Based on BP Ranges 

2 Types of Hypertension (based on etiology) 

Primary (Essential) Hypertension 

• 90-95% of cases
• No specific cause
• Related to
  • Obesity
  • ↑Cholesterol
  • Atherosclerosis
  • ↑Salt Diet
  • Diabetes
  • Stress
  • Family History
  • Smoking
• Diastolic Hypertension
  • Elevated diastolic pressure
  • Relatively normal systolic (or slightly elevated)
  • Mostly middle-aged men
• Isolated Systolic Hypertension
  • Elevated systolic pressure
  • Normal diastolic pressure
    • i.e., High Pulse Pressure
  • In older adults (60 years+)
    • May be due to reduced compliance of the aorta with increasing age
  • In younger adults (17-25 years)
    • May be due to overactive sympathetic NS → ↑Cardiac Output
    • Or congenitally stiff/narrow aorta

Secondary (Inessential) Hypertension

• 5-10% of cases 
• Secondary to another disease, e.g.:
  • Renal disease 
  • Endocrine disorders 
  • Pregnancy (pre-eclampsia)
    • In 10% of pregnancies 
    • 20 weeks of gestation 
  • Others: cancer, drugs, alcohol 

Organ Damage Caused by Hypertension 

Heart 

• Increased afterload
  • ↑ Workload of Heart → ↑Afterload → Pumps Harder → Hypertrophy → Failure
• Left ventricular hypertrophy
  • To compensate for higher workload
  • Compromised L-Ventricular Volume → ↓Stroke Volume →↓Cardiac Output

Lungs 

• Pulmonary congestion 
• Backing up of blood in pulmonary circuit 
• Why? ↑BP = ↑Aortic-BP = ↑Afterload = ↓SV = ↑ESV = ↓Pulmonary Blood Flow

Cerebrovascular 

• Stroke – typically intracerebral hemorrhage 
• Rupture of artery/arterioles in the brain 

See image on right-hand side

Aorta/Peripheral Vascular 

• Arterial mechanical damage (e.g., aneurysms/dissecting aneurysms) 
• Accelerated atherosclerosis

Kidneys 

• Nephrosclerosis (hardening of kidney blood vessels) 
• Renal failure 

Short-term Physiological Control of Blood Pressure 

The Baroreceptor Reflex 

Risk Factors of Hypertension 

Age

• Blood pressure normally increases with age
  • Baby: 50/40
  • Child: 100/60
  • Adult: 120/80
  • Aged: 150/85 (quite normal) 
• Due to the loss of elasticity of blood vessels (decreased compliance) 
• Atherosclerosis 

Race

Obesity 

• Fatty diet → atherosclerosis
• Body fat → kms more vessels → ↑Peripheral Resistance → Hypertension
• Physical weight of fat may impede venous return
• Kidney dysfunction → loss of long-term BP (blood volume) control

Excess Na⁺ Intake 

• If normal kidney function
  • Na⁺ intake → slight BP increase (due to fluid retention) 
  • But excess Na⁺ intake and H₂O excreted by kidneys → BP returns to normal 
• If impaired kidney function
  • Na⁺ intake → larger BP increase 
  • Because excess Na⁺ and H₂O not excreted by kidneys (less efficiently) 

Basic Hypertension Treatment Plan

Anti-Hypertensive Drug Mechanisms 

• Diuretics
  • Increase urination → decrease blood volume 
  • Aim: reduce workload on heart by reducing preload 
• Sympatholytics
  • Reduces sympathetic activity (Prevents ↑HR/↑Contractility = Decrease in CO)
  • e.g., beta blockers 
• Vasodilators
  • Reduce peripheral resistance
  • Reduce afterload
  • Reduce workload on the heart 
• Renin-Angiotensin Antagonists (ACE Inhibitors)
  • Decreases effects of Renin-Angiotensin System
    • Decreases sympathetic drive 
    • Decreases vasoconstriction
    • Decreases fluid retention
    • Decreases preload 
    • Decreases afterload 

Physiology of Shock

Shock 

• Profound hemodynamic/metabolic disorder due to inadequate blood flow and O₂ delivery 
• Common causes of shock 
  • Hypovolemic change
    • Severe dehydration 
    • Hemorrhage 
  • Cardiogenic change
    • Heart failure (heart isn’t getting enough blood out) 
    • Decreased venous return 
  • Distributive alteration
    • Excessive metabolism (i.e., even a normal CO is inadequate) 
    • Abnormal perfusion patterns (i.e., most of CO perfuses tissues other than those in need) 
    • Neurogenic shock (i.e., sudden loss of vasomotor tone → massive venodilation) 
    • Anaphylactic shock (drastic decrease in CO & BP due to allergic reaction) 
    • Septic shock (disseminated bacterial infection in the body → extensive tissue damage) 

3 Stages of Shock 

Non-Progressive 

• Stable, not self-perpetuating
• Symptoms
  • Hypotension (Low BP)
  • Tachycardia (High HR – body’s attempt to compensate for poor perfusion)
  • Tachypnea (High breathing-rate – phrenic nerve stimulation – diaphragm)
  • Oliguria (Low urine production by kidney)
  • Clammy skin
  • Chills
  • Restlessness
  • Altered consciousness
  • Allergy symptoms (if anaphylaxis)
• The body’s compensatory mechanisms (below) will prevail without intervention.
  • Aim to increase BP

Progressive Stage 

• Unstable, vicious cycle of cardiovascular deterioration – self-perpetuating
• Compensatory mechanisms are insufficient to raise BP
• Perfusion continues to fall → organs become more ischemic (heart → failure)
  • Cardiac depression (due to O₂ Deficit to Heart)
  • Vasomotor failure (due to O₂ Deficit to Brain)
  • “Sludged blood” (viscosity ↑ – harder to move)
  • Increased capillary permeability
• Symptoms
  • Beginning of organ failure
  • Severely altered consciousness
  • Marked bradycardia (initially tachycardic – but now the body is giving up)
  • Tachypnea (fast breathing) with dyspnea (no breathing)
  • Cold, lifeless skin
  • Acidosis – (CO₂ equation affected)
• Treatment
  • Identify & remove causative agents
  • Volume replacement for hypovolemia
  • If septic shock: antibiotics
  • Sympathomimetic drugs: if neurogenic shock (loss of vasomotor tone – vasodilation)
• Fatal if untreated